Modulation of Gardos channel activity by cytokines in sickle erythrocytes

Modulation of Gardos channel activity by cytokines in sickle erythrocytes
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DOI:
10.1182/blood.v99.1.357
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发表时间:
2002-01-01
期刊:
影响因子:
20.3
通讯作者:
Brugnara, C
Brugnara, C
中科院分区:
医学1区
文献类型:
--
作者:
Rivera, A;Jarolim, P;Brugnara, C

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It has recently been shown that the Gardos channel activity of mouse erythrocytes can be modified by endothelins, suggesting a functional linkage between endothelin receptors and the Gardos channel. Using (86)Rubidium (Rb-86) influx, effects were estimated of proinflammatory molecules such as platelet activator factor (PAF), endothelin-1 (ET-1), interleukin-10 (IL-10), and regulated on activation normal T cells expressed and secreted (RANTES) on the Gardos channel activity in human normal and sickle red cells. It was found that PAF (EC50: 15 +/- 7 nM), RANTES (EC50, 9 +/- 6 ng/mL [1.2 +/- 0.8 nM]), IL-10 (EC50, 11 +/- 8 ng/mL [204 +/- 148 nM]), and ET-10 (EC50,123 +/- 34 nM) induce a significant increase in Gardos channel activity-between 28% and 84%-over the control. In addition, these agents modify the Gardos channel affinity for internal Ca++ (K-0.5) by 2- to 6-fold. Biochemical evidence is provided for the presence of ET receptor subtype B in sickle and normal red cells. Furthermore, it was found that ET-1, PAF, RANTES, and IL-10 induce a significant increase in red cell density (P